Interim Analysis of Dara VRD in the Treatment of TE-NDMM Patients with Standard Risk Who Refused to Accept ASCT As First Line in China

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.1997-1997
• Main Authors: Fu, Chengcheng, Wang, Jing, Jin, Song, Yan, Lingzhi, Shang, Jingjing, Yao, Weiqin, Shi, Xiaolan, Yan, Zhi, Wu, Depei
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-209260

Background: In China, the utilization rate of ASCT as front-line therapy is merely 10%. Many transplant-eligible (TE) patients decline ASCT for various subjective and objective reasons. Recent studies, such as GRIFFIN (D-VRd) and CASSIOPEIA (D-VTd), have shown promising results in TE-NDMM patients receiving ASCT as initial therapy. These findings have prompted us to investigate the potential efficacy of D-VRd in standard-risk patients. This interim analysis presents the first open-label, single-arm study evaluating the efficacy and safety of D-VRd in TE-NDMM patients with standard risk who declined ASCT in China (NCT 05088330). Methods: We enrolled NDMM patients, as per IMWG criteria, who were transplant-eligible but voluntarily declined ASCT. Patients with t(4;14), Del(17p), t(14;16), or R-ISS stage III were excluded. The D-VRd regimen consisted of: Daratumumab: 16 mg/kg I.V. weekly for 2 cycles, then every 3 weeks for 6 more cycles, bortezomib: 1.3 mg/m2 SC, Days 1, 4, 8, 11 for 8 cycles, lenalidomide: 25 mg P.O., Days 1-14 for 8 cycles, dexamethasone: 20 mg P.O., Days 1, 2, 4, 5, 8, 9, 11, 12 for 8 cycles. Patients then received Daratumumab 16mg/kg I.V. monthly for 1 year as maintenance therapy. The primary endpoint was NGS MRD negativity at 10-5 after 8 cycles of D-VRd. Secondary objectives included ORR, sCR, ≥CR, ≥VGPR, AEs, TTR, and DOR. Stem cell collection was recommended after 4 cycles of D-VRd. Result: As of June 30, 2024, 46 patients were enrolled in the study. The median age was 62 years (range: 38-74), with 23 (50.0%) male patients. Cytogenetic analysis revealed 27 (58.7%) patients with 1q gain (3 copies) and 4 (8.7%) patients with t(11;14). Additionally, 8 (17.4%) patients presented with renal insufficiency, and 6 (13%) had extramedullary disease (EMD). The overall response rate (ORR) was 97.4%, with 89.7% of patients achieving VGPR or better. Notably, 64.1% of patients attained CR or sCR. The median duration of treatment was 10 months (range: 1-21). The median number of treatment cycles was 9. Post-induction stem cell collection and storage was successful underwent in 19 (41.3%) patients. With a median follow-up of 12 months (range: 1-23), 72.7% (16/22) of patients achieved NGS MRD negativity after 8 cycles. Subgroup analysis comparing patients with 1q gain versus those without showed ORR, CR+sCR, and 1-year progression-free survival (PFS) rates of 95.8%, 58.3%, and 88.2% versus 100%, 73.3%, and 100%, respectively (p>0.01). Treatment-related